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BACKGROUND: Thromboembolic events (TE) associated with left ventricular (LV) thrombus (LVT) are of clinical concern; however, further investigation into their prevalence and risk predictors is warranted. METHODS: We retrospectively identified 256 patients diagnosed with LVT by echocardiography between 2010 and 2021. The primary outcome was the occurrence of TE, including stroke and arterial thromboembolism. Patients were divided into TE (+) and TE (-) groups for clinical comparison, with a focus on factors related to TE. RESULTS: The TE event rate was 9% over a median period of 4±3 years. Notably, most TE occurred within 3 months and became scarce after 2 years of follow-up; based on this, LVT chronicity was defined as LVT persistency for ≥2 years. A prior TE history proved to be a positive predictor of TE (hazard ratio, HR:5.92, Confidence Interval, CI:1.45-24.18, p=0.01), while LVT chronicity showed to be a negative predictor (HR:0.04, CI:0.01-0.15, p<0.001). LVT chronicity accurately predicted TE (area under curve of 0.86 [95% CI: 0.80-0.93], cutoff value of 794 days [sensitivity: 69%, specificity: 91%]). CONCLUSION: TE associated with LVT occurs in the early period of recognition, and a history of TE is an independent predictor for future TE. Once LVT becomes chronic (≥2 years), TE is rare.
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BACKGROUND: Although several biomarkers exist for patients with heart failure (HF), their use in routine clinical practice is often constrained by high costs and limited availability. OBJECTIVE: We examined the utility of an artificial intelligence (AI) algorithm that analyzes printed electrocardiograms (ECGs) for outcome prediction in patients with acute HF. METHODS: We retrospectively analyzed prospectively collected data of patients with acute HF at two tertiary centers in Korea. Baseline ECGs were analyzed using a deep-learning system called Quantitative ECG (QCG), which was trained to detect several urgent clinical conditions, including shock, cardiac arrest, and reduced left ventricular ejection fraction (LVEF). RESULTS: Among the 1254 patients enrolled, in-hospital cardiac death occurred in 53 (4.2%) patients, and the QCG score for critical events (QCG-Critical) was significantly higher in these patients than in survivors (mean 0.57, SD 0.23 vs mean 0.29, SD 0.20; P<.001). The QCG-Critical score was an independent predictor of in-hospital cardiac death after adjustment for age, sex, comorbidities, HF etiology/type, atrial fibrillation, and QRS widening (adjusted odds ratio [OR] 1.68, 95% CI 1.47-1.92 per 0.1 increase; P<.001), and remained a significant predictor after additional adjustments for echocardiographic LVEF and N-terminal prohormone of brain natriuretic peptide level (adjusted OR 1.59, 95% CI 1.36-1.87 per 0.1 increase; P<.001). During long-term follow-up, patients with higher QCG-Critical scores (>0.5) had higher mortality rates than those with low QCG-Critical scores (<0.25) (adjusted hazard ratio 2.69, 95% CI 2.14-3.38; P<.001). CONCLUSIONS: Predicting outcomes in patients with acute HF using the QCG-Critical score is feasible, indicating that this AI-based ECG score may be a novel biomarker for these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01389843; https://clinicaltrials.gov/study/NCT01389843.
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Inteligencia Artificial , Biomarcadores , Electrocardiografía , Insuficiencia Cardíaca , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Aguda , Biomarcadores/sangre , Electrocardiografía/métodos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Pronóstico , Estudios Prospectivos , República de Corea , Estudios RetrospectivosRESUMEN
BACKGROUND: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5-10% (termed as borderline-QRISK3 group) using the UK Biobank. METHODS: Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. RESULTS: Among 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30-1.52) with a 13.1% (95% CI, 11.7-14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010-0.017) in non-statin cohort, 0.013 (0.007-0.019) in stage 1 hypertension cohort, and 0.023 (0.018-0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3. CONCLUSIONS: Reti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.
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Enfermedades Cardiovasculares , Aprendizaje Profundo , Hipertensión , Adulto , Persona de Mediana Edad , Humanos , Enfermedades Cardiovasculares/epidemiología , Bancos de Muestras Biológicas , Factores de Riesgo , Reino Unido/epidemiología , Hipertensión/complicaciones , BiomarcadoresRESUMEN
RATIONALE & OBJECTIVE: The association between short-term blood pressure variability (BPV) and kidney outcomes is poorly understood. This study evaluated the association between short-term BPV and kidney disease outcomes in people with hypertension. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,173 hypertensive participants in the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (2013-2018) Study with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. EXPOSURE: Short-term BPV assessed by average real variability (ARV). OUTCOME: Composite kidney disease outcome (30% decline in eGFR from baseline, new occurrence of eGFR <60mL/min/1.73m2, or onset of UACR >300mg/g). ANALYTICAL APPROACH: Multivariable Cox regression analyses to evaluate the association between systolic and diastolic BP ARV (SBP-ARV and DBP-ARV) and outcomes. RESULTS: During a median follow-up of 5.4 [4.1-6.5] years, 271 events of the composite kidney disease outcome occurred (46.5 per 1,000 person-years). Multivariable Cox analysis revealed that the highest SBP-ARV and DBP-ARV tertiles were associated with a higher risk of the composite kidney disease outcome than the lowest tertiles, independent of the 24-hour SBP or DBP levels (HR, 1.64 [95% CI, 1.16-2.33], and 1.60 [95% CI, 1.15-2.24] for SBP-ARV and DBP-ARV, respectively). These associations were consistent when SBP-ARV and DBP-ARV were treated as continuous variables (HR per 1.0-unit greater SBP-ARV, 1.03 [95% CI, 1.01-1.06]; HR per 1.0-unit greater DBP-ARV, 1.04 [95% CI, 1.01-1.08]). These associations were consistent, irrespective of subgroups (age, sex, 24-hour SBP or DBP, and moderate albuminuria). However, other measures of short-term BPV including SD, coefficient of variation, and dipping patterns were not associated with the composite kidney disease outcome. LIMITATIONS: Observational study design, the use of single measurement of 24-hour BP, lack of information on changes in antihypertensive medication during the follow-up. CONCLUSIONS: Short-term BPV is associated with the development of a composite kidney disease outcome in hypertensive patients.
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Hipertensión , Fallo Renal Crónico , Humanos , Presión Sanguínea/fisiología , Estudios Prospectivos , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/complicaciones , Fallo Renal Crónico/terapiaRESUMEN
Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.
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Antihipertensivos , Presión Sanguínea , Estado Funcional , Accidente Cerebrovascular Isquémico , Trombectomía , Anciano , Femenino , Humanos , Presión Sanguínea/efectos de los fármacos , Hemorragia Cerebral/etiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Trombectomía/métodos , Procedimientos Endovasculares , Enfermedad Aguda , Resultado del Tratamiento , Masculino , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéuticoRESUMEN
BACKGROUND: Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. METHODS: A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis). RESULTS: The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group. CONCLUSIONS: Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.
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Diabetes Mellitus , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Masculino , Conejos , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Fibrosis , Glucósidos/farmacología , Glucósidos/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
BACKGROUND: High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF). METHODS: The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge. RESULTS: The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan-Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P < 0.001). Multivariate Cox proportional analysis showed that high GV was associated with an increased risk of 1-year (HR 1.56, 95% CI 1.26-1.92) mortality. High GV significantly increased the risk of 1-year mortality in non-diabetic patients (HR 1.93, 95% CI 1.47-2.54) but not in diabetic patients (HR 1.19, 95% CI 0.86-1.65, P for interaction = 0.021). CONCLUSIONS: High in-hospital GV before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic patients with acute HF.
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Insuficiencia Cardíaca , Hiperglucemia , Humanos , Masculino , Anciano , Femenino , Glucemia , Volumen Sistólico , Pronóstico , Función Ventricular Izquierda , Hospitalización , HospitalesRESUMEN
BACKGROUND: ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). OBJECTIVE: we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. METHODS: we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). RESULTS: in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42-1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69-3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31-1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14-1.69]) and 18% (HR = 1.18 [1.10-1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). CONCLUSIONS: the DL-derived RetiAGE provides a novel, alternative approach to measure ageing.
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Aprendizaje Profundo , Anciano , Envejecimiento/fisiología , Humanos , Morbilidad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We investigated the superiority of MAFLD versus NAFLD in predicting the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: A total of 2,144 subjects without a history of ASCVD, who underwent a comprehensive medical health check-up, were selected for the study. The associations between fatty liver status and coronary risk surrogates, such as coronary artery calcium score (CACS), coronary artery disease, quantitative stenosis grade, and 10-year ASCVD risk, were analyzed. RESULTS: MAFLD and NAFLD were identified in 995 (46.4%) and 891 (41.6%) subjects, respectively. Subjects with MAFLD or NAFLD were more likely to be male and had a significantly higher prevalence of central obesity, obesity, hypertension, diabetes, and dyslipidemia (all, p < 0.05) than their counterparts. In terms of coronary risk surrogates, the MAFLD or NAFLD population had a significantly higher proportion of subjects with CACS > 100, coronary artery disease, higher grade of coronary artery stenosis, and higher 10-year ASCVD risk (all, p < 0.05) than their counterparts. Multivariable logistic regression models showed an independent association between MAFLD/NAFLD and coronary risk surrogates (all, p < 0.05). However, NAFLD only, defined as 'NAFLD, but not MAFLD,' was not associated with an increased coronary risk, compared to MAFLD. CONCLUSIONS: Although both MAFLD and NAFLD discriminated different ASCVD risks, MAFLD predicted the risk of ASCVD better than NAFLD in asymptomatic subjects who underwent medical health check-ups.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Enfermedad del Hígado Graso no Alcohólico , Calcio , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Endotelio Vascular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Remodelación Vascular , Animales , Proteínas Reguladoras de la Apoptosis/genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/patología , HDL-Colesterol/genética , HDL-Colesterol/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Endotelio Vascular/patología , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Ratones , Ratones Noqueados , Proteínas de Neoplasias/genética , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación/genética , Proteínas Proto-Oncogénicas c-akt/genéticaRESUMEN
The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing rapidly, and its prognosis is as poor as that of HF with reduced EF. Hypertension is an important risk factor involved in the pathophysiology of HFpEF. Although treatment of hypertension lowers the incidence of HF and is beneficial in patients with HFpEF, there is conflicting evidence on this topic. This article discusses the pathophysiological mechanisms linking hypertension with HFpEF and also the current evidence on the treatment of hypertension in patients with HFpEF.
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Presión Sanguínea/fisiología , Manejo de la Enfermedad , Insuficiencia Cardíaca/fisiopatología , Hipertensión/complicaciones , Volumen Sistólico/fisiología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Hipertensión/fisiopatología , Hipertensión/terapia , Incidencia , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Survivin has an anti-apoptotic effect against anthracycline-induced cardiotoxicity. Clinically, statin use is associated with a lower risk for heart failure in breast cancer patients with anthracycline chemotherapy. So, the purpose of our study was to investigate whether survivin mediates the protective effect of statin against anthracycline-induced cardiotoxicity. METHODS: Mice were treated once a week with 5 mg/kg doxorubicin for 4 weeks with or without atorvastatin 20 mg/kg every day then heart tissues were analyzed. Molecular and cellular biology analyses were performed with H9c2 cell lysates. RESULTS: Doxorubicin suppressed survivin expression via activation of FOXO1 in H9c2 cardiomyocytes. Whereas, atorvastatin inhibited FOXO1 by increasing phosphorylation and inhibiting nuclear localization. Doxorubicin induced FOXO1 binding to STAT3 and prevented STAT3 from interacting with Sp1. However, atorvastatin inhibited these interactions and stabilized STAT3/Sp1 transcription complex. Chromatin immunoprecipitation analysis demonstrated that doxorubicin decreased STAT3/Sp1 complex binding to survivin promoter, whereas atorvastatin stabilized this binding. In mouse model, atorvastatin rescued doxorubicin-induced reduction of survivin expression and of heart function measured by cardiac magnetic resonance imaging. CONCLUSIONS: Our study suggested a new pathophysiologic mechanism that survivin mediated protective effect of atorvastatin against doxorubicin-induced cardiotoxicity via FOXO1/STAT3/Sp1 transcriptional network.
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Atorvastatina/farmacología , Cardiotónicos/farmacología , Citoprotección , Doxorrubicina/toxicidad , Proteína Forkhead Box O1/antagonistas & inhibidores , Miocitos Cardíacos/metabolismo , Survivin/metabolismo , Animales , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Citoprotección/efectos de los fármacos , Modelos Animales de Enfermedad , Proteína Forkhead Box O1/metabolismo , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Factor de Transcripción Sp1/metabolismo , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/efectos de los fármacosRESUMEN
BACKGROUND: Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. METHODS: Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. RESULTS: Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages. CONCLUSIONS: In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of ≥ 70.
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Presión Sanguínea , Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Adulto , Factores de Edad , Anciano , Bases de Datos Factuales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de TiempoRESUMEN
Continuous positive airway pressure (CPAP) therapy may decrease left ventricular (LV) loads and improve myocardial oxygenation. In this study, we investigated the effect of CPAP on LV diastolic function compared with sham treatment in patients with severe obstructive sleep apnoea (OSA).This 3-month prospective single-centre randomised sham-controlled trial analysed 52 patients with severe OSA. Patients were randomly assigned (1:1) to receive either CPAP or sham treatment for 3â months. The main investigator and patients were masked to the trial randomisation. The primary end-point was change of early diastolic mitral annular (e') velocity over the 3-month period. Secondary end-points were pulse wave velocity (PWV), 24-h ambulatory blood pressure (BP) and variables of ventricular-vascular coupling at 3â months.After 3â months of follow-up, CPAP treatment significantly increased the e' velocity, and was greater than the sham treatment (0.65±1.70 versus -0.61±1.85â cm·s-1, p=0.014). The PWV, 24-h mean diastolic BP, night-time diastolic BP, arterial elastance index and ventricular-vascular coupling index after 3â months of follow-up decreased significantly in the CPAP group.In patients with severe OSA, CPAP treatment for 3â months improved LV diastolic function more than sham treatment, and was accompanied by improvements in arterial stiffness and ventricular-vascular coupling.
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Presión de las Vías Aéreas Positiva Contínua , Ventrículos Cardíacos/fisiopatología , Apnea Obstructiva del Sueño/terapia , Función Ventricular Izquierda , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Diástole , Ecocardiografía de Estrés , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Análisis de la Onda del Pulso , República de Corea , Rigidez VascularAsunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Femenino , Glucósidos/farmacología , Humanos , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Resultado del TratamientoRESUMEN
BACKGROUND: The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins. METHODS: Thirty two patients were initially screened and HDLs of 21 patients were finally analyzed. Patients were randomized to receive atorvastatin 20 mg (n = 11) or atorvastatin 5 mg/ezetimibe 10 mg combination (n = 10) for 8 weeks. The cholesterol efflux capacity and other anti-inflammatory functions were assessed based on HDLs of the participants before and after treatment. Pre-specified HDL proteins of the same HDL samples were measured. RESULTS: The post-treatment increase in cholesterol efflux capacities was similar between the groups (35.6% and 34.6% for mono-therapy and combination, respectively, p = 0.60). Changes in nitric oxide (NO) production, vascular cell adhesion molecule-1 (VCAM-1) expression, and reactive oxygen species (ROS) production were similar between the groups. The baseline cholesterol efflux capacity correlated positively with apolipoprotein (apo)A1 and C3, whereas apoA1 and apoC1 showed inverse associations with VCAM-1 expression. The changes in the cholesterol efflux capacity were positively correlated with multiple HDL proteins, especially apoA2. CONCLUSIONS: Two regimens increased the cholesterol efflux capacity of HDL comparably. Multiple HDL proteins, not limited to apoA1, showed a correlation with HDL functions. These results indicate that conventional lipid therapy may have additional effects on HDL functions with changes in HDL proteins. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02942602 .
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Apolipoproteínas/sangre , Atorvastatina/uso terapéutico , HDL-Colesterol/sangre , Ezetimiba/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Anticolesterolemiantes/farmacología , Atorvastatina/farmacología , Quimioterapia Combinada , Ezetimiba/farmacología , Femenino , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
The spring-in phenomenon of the composite parts can affect the assembly process. This study aims to predict the spring-in phenomenon of a carbon fiber reinforced plastic (CFRP) part. Here, we predict the spring-in of the CFRP part using a coupled analysis of the forming and cooling processes during the stamping process. First, a simulation of the entire forming process, such as the transfer of the composite laminate, gravity analysis, and forming was performed to obtain the temperature distribution of the CFRP part. Subsequently, a finite-element (FE) simulation of the cooling process was conducted to predict the spring-in phenomenon of the shaped CFRP part using the temperature data obtained in the forming simulation. Finally, a CFRP part was manufactured and compared with the results of the FE simulation.
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This study investigates the secondary bonding of aircraft skin/stiffener assemblies using press conduction welding with carbon fiber/polyetherketoneketone thermoplastic composites and polyetherimide adhesive. Recognizing the challenges posed by conventional welding methods in maintaining material integrity and uniformity, this research explores an alternative methodology that mitigates these issues while ensuring high-strength bonds. The press conduction welding parameters were selected based on single-lap shear tests and applied in the bonding of skin and omega stiffener components. The temperature range was determined using differential scanning calorimetry. The pressure was held at 1 MPa for 180 s. The welding temperature that produced a high-bonding strength was identified experimentally; these key variables were then used in the welding process of the skin and omega stiffener. By analyzing how the fibers tear and the effectiveness of interdiffusion between the plies, we were able to gain insights into the bonding strength and fractured surface. The findings suggest that press conduction welding provides a viable route for secondary bonding in thermoplastic composite structures, highlighting its advantages in terms of processing efficiency and integrity. This study contributes to the understanding of the mechanical behaviors of bonded joints and underscores the significance of temperature control in the welding process.
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BACKGROUND AND OBJECTIVES: Although cardiac rehabilitation (CR) is highly recommended in patients with cardiovascular disease (CVD), participation in CR is low mainly due to access barriers. Home-based CR (HBCR) has been recommended to overcome access barriers. Exercise is a core component of CR and should be developed and implemented based on individual characteristics. We aimed to assess physical activity behaviors, exercise preferences, and exercise barriers to understand physical activity characteristics of CVD patients. METHODS: Participants were patients between the ages 19 to 75 years with a history of heart failure with reduced ejection fraction (HFrEF) or myocardial infarction (MI). They completed a cross-sectional survey at a tertiary hospital's outpatient clinic from April to June 2021. Survey data included physical activity levels, patterns, preference, and barriers of exercise. RESULTS: Participants (n=189; 143 males, 46 females, 62.1±12.0 years) were diagnosed as either HFrEF (n=160, 84.7%) or a history of MI (n=97, 51.3%). Only 26.5% of patients engaged in moderate to vigorous exercise for more than 150 minutes per week. Participants preferred exercising alone or with families. Walking (65.6%) and resistance exercises (35.4%) were favored, with outdoor (37%) and home-based (30.2%) settings preferred over fitness centers (10.6%) and hospitals (0.5%). Barriers to exercise included fatigue (34.4%), poor health perception (31.7%), and low fitness levels (30.7%). CONCLUSIONS: The results of this study can be used to develop tailored HBCR programs that consider individual preferences and address specific barriers, facilitating adequate physical activity engagement.
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Although increase in physical activity is important to improve prognosis of cardiac patients in addition to hospital-based exercise cardiac rehabilitation, their physical activity levels are not properly understood. This study aimed to examine domain- and intensity-specific physical activity in individuals with coronary heart disease (CHD) and compare them with non-CHD individuals. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2019 were analyzed, including 1083 CHD patients and 38,532 non-CHD individuals. The inclusion criteria were age 19 years or older and data not missing for CHD information. Before and after propensity score matching (PSM) for age, sex, body mass index, education, household income, alcohol intake, and smoking status, domain (leisure, work, transportation)-and intensity (moderate, vigorous) -specific physical activity participation levels were compared between individuals with and without CHD. Before PSM, CHD individuals were older, less educated, more sedentary, and participated less in PAs compared to non-CHD individuals. After PSM, CHD individuals had similar levels of domain-specific PAs. However, they had higher work-related PA levels (29.7 ± 209.6 vs. 42.1 ± 291.3 min/week p = 0.022) and more sedentary time (487.2 ± 224.2 vs. 514.1 ± 228.7. p = 0.003) than those without CHD. Subgroup analysis revealed lower leisure-related PA in men with CHD (63.5 ± 165.5 vs. 47.3 ± 140.2, p < 0.05) and higher work-related PA in women with CHD (18.9 ± 159.7 vs. 57.1 ± 397.5, p < 0.01). Among those < 65 years of age, individuals with CHD spent more time sedentary than individuals without CHD. CHD individuals are not physically inactive compared with non-CHD individuals who are similar in sociodemographic status and lifestyle. CHD patients' PA levels may have been underestimated.